U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H25O10P.2Na
Molecular Weight 514.3705
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MINNELIDE

SMILES

[Na+].[Na+].[H][C@@]12C[C@@H]3O[C@@]34[C@H](OCOP([O-])([O-])=O)[C@]5(O[C@H]5[C@@H]6O[C@]46[C@@]1(C)CCC7=C2COC7=O)C(C)C

InChI

InChIKey=ZHBJMVNZRZUQEP-KIKMAQITSA-L
InChI=1S/C21H27O10P.2Na/c1-9(2)19-14(30-19)15-21(31-15)18(3)5-4-10-11(7-26-16(10)22)12(18)6-13-20(21,29-13)17(19)27-8-28-32(23,24)25;;/h9,12-15,17H,4-8H2,1-3H3,(H2,23,24,25);;/q;2*+1/p-2/t12-,13-,14-,15-,17+,18-,19-,20+,21+;;/m0../s1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C21H25O10P
Molecular Weight 468.391
Charge -2
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 9 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects. Triptolide is a woody vine which is widely distributed in Eastern and Southern China. In China, triptolide is frequently used to treat autoimmune and/or inflammatory diseases due to its favorable cost–benefit ratio. Commercial preparations of triptolide have been commonly used for the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and psoriasis.Triptolide has been demonstrated to exert novel chondroprotective and anti-inflammatory effects on rheumatoid arthritis. Triptolide has been used to treat ADPKD patients in clinical trials in China. Triptolide significantly protected glomerular filtration rate (eGFR) of ADPKD patients compared with placebo. Two recent small clinical studies have demonstrated tiptolide’s effectiveness against rheumatoid arthritis. A larger study confirmed the therapeutic effects of triptolide in the aforementioned studies. Triptolide is among the most powerful and broadly active antiinflammatory/immunomodulating natural products ever discovered. Triptolide acts at nanomolar concentrations and inhibits the production of various cellular targets including inflammatory cytokines, cyclooxygenase, inducible nitric oxide synthase and metalloproteinases and transcription factors. The anti-tumor activity of Triptolide in vitro and in various tumor-bearing animal models has been investigated for years, and many findings showed that Triptolide is a promising agent in anti-tumor therapy. Triptolide has been approved for Phase I clinical trials for the treatment of prostate cancer, but the anti-tumor effect and mechanism of TPL need to be further elucidated.

CNS Activity

Curator's Comment: Triptolide crosses the blood-brain barrier easily due to its small molecular size and lipophilic property. Triptolide inhibits amyloid-β production and protects neural cells by inhibiting CXCR2 activity.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
14.18 µM [IC50]
8.36 µM [IC50]
Target ID: HuCCT1, human cholangiocarcinoma
12.6 nM [IC50]
30.0 pM [IC50]
14.0 nM [IC50]
Conditions
OverviewDrug as perpetrator​Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis.
2001 Mar
Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.
2002 Jan 15
Triptolide suppresses CD80 and CD86 expressions and IL-12 production in THP-1 cells.
2005 Feb
[Study of triptolide-induced apoptosis in MUTZ-1 cells and its allied mechanism].
2005 Jun
Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells.
2006 Jul 17
Triptolide binds covalently to a 90 kDa nuclear protein. Role of epoxides in binding and activity.
2007
Triptolide upregulates NGF synthesis in rat astrocyte cultures.
2007 Jul
Differential expression and oxidation of MKP-1 modulates TNF-alpha gene expression.
2007 Sep
Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells.
2008 Dec
Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis.
2008 Feb
Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro.
2008 Sep
Phase I dose-escalation study of F60008, a novel apoptosis inducer, in patients with advanced solid tumours.
2009 Jul
Caspase 3 is involved in the apoptosis induced by triptolide in HK-2 cells.
2009 Jun
Interleukin-6-independent expression of glucocorticoid receptor is upregulated by triptolide in multiple myeloma.
2009 May
Heat shock protein 72 protects kidney proximal tubule cells from injury induced by triptolide by means of activation of the MEK/ERK pathway.
2009 May-Jun
Sex differences in subacute toxicity and hepatic microsomal metabolism of triptolide in rats.
2010 Apr 30
Effects of cytochrome P4503A inducer dexamethasone on the metabolism and toxicity of triptolide in rat.
2010 Feb 1
Triptolide alters histone H3K9 and H3K27 methylation state and induces G0/G1 arrest and caspase-dependent apoptosis in multiple myeloma in vitro.
2010 Jan 12
Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation.
2010 Jun
Physio-pathological parameters affect the activation of inflammatory pathways by deoxynivalenol in Caco-2 cells.
2010 Oct
Knockout of hepatic P450 reductase aggravates triptolide-induced toxicity.
2011 Aug 10
Cytotoxicity of Triptolide and Triptolide loaded polymeric micelles in vitro.
2011 Dec
Effect of triptolide on progesterone production from cultured rat granulosa cells.
2012 Jun
Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells.
2012 Mar
Role of Nrf2 in protection against triptolide-induced toxicity in rat kidney cells.
2012 Sep 3
Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo.
2013
Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats.
2013 Aug
Establishment of hypoxia induction in an in vivo animal replacement model for experimental evaluation of pancreatic cancer.
2014 Jul
Triptolide-induced oxidative stress involved with Nrf2 contribute to cardiomyocyte apoptosis through mitochondrial dependent pathways.
2014 Nov 4
Interleukin-17 mediates triptolide-induced liver injury in mice.
2014 Sep
Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice.
2015 Jul 2
Triptolide disrupts fatty acids and peroxisome proliferator-activated receptor (PPAR) levels in male mice testes followed by testicular injury: A GC-MS based metabolomics study.
2015 Oct 2
Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells.
2015 Oct 5
Suppression of the migration and invasion is mediated by triptolide in B16F10 mouse melanoma cells through the NF-kappaB-dependent pathway.
2016 Dec
Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer.
2017
PG490-88, a derivative of triptolide, suppresses ischemia/reperfusion-induced lung damage by maintaining tight junction barriers and targeting multiple signaling pathways.
2019 Mar
Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia.
2019 May 20
Patents

Sample Use Guides

Minnelide will be administered at the dose of 0.67 mg/m2 as a 30 min infusion intravenously daily on days 1-21 of each cycle followed by a 7 day rest period (days 22-28)
Route of Administration: Intravenous
The A549/Taxol cells were treated with different concentrations of Triptolide (0.03, 0.3 or 3 uM/l) for 2, 4, 6 and 12 h. On exposure to 3 uM Triptolide for 2, 4, 6 and 12 h, the extent of cell apoptosis observed markedly increased. The inhibitory effect reached a maximum with 3 uM Triptolide at the 12 h time point (cell apoptotic rate, 65.33%), whereas the apoptotic rate of the control group was 7.23% at 12 h.
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:17:57 GMT 2023
Edited
by admin
on Sat Dec 16 09:17:57 GMT 2023
Record UNII
1CIV2UMO40
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MINNELIDE
Common Name English
14-O-PHOSPHONOOXYMETHYLTRIPTOLIDE DISODIUM SALT
Common Name English
TRISOXIRENO(4B,5:6,7:8A,9)PHENANTHRO(1,2-C)FURAN-1(3H)-ONE, 3B,4,4A,6,6A,7A,7B,8B,9,10-DECAHYDRO-8B-METHYL-6A-(1-METHYLETHYL)-6-((PHOSPHONOOXY)METHOXY)-, SODIUM SALT (1:2), (3BS,4AS,5AR,6R,6AS,7AS,7BS,8AS,8BS)-
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 388512
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
FDA ORPHAN DRUG 471615
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
Code System Code Type Description
CAS
1254702-87-8
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
PRIMARY
PUBCHEM
46203139
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
PRIMARY
NCI_THESAURUS
C111762
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
PRIMARY
FDA UNII
1CIV2UMO40
Created by admin on Sat Dec 16 09:17:57 GMT 2023 , Edited by admin on Sat Dec 16 09:17:57 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE